Garlic-derived anticancer agents: structure and biological activity of ajoene

Abstract

Garlic has been used throughout the centuries to treat infections, heart disease, and cancer. Ajoene is one of the main compounds formed from heating crushed garlic as a mixture of E- and Z-isomers (E- and Z-4,5,9-trithiadodeca-1,6,11-triene 9-oxide). Ajoene possesses a broad spectrum of biological activities that include anticancer activity. It's cytotoxicity towards cancer cells is postulated to occur via an apoptotic mechanism involving activation of the mitochondrial-dependent caspase cascade. Structure-activity studies on ajoene and ajoene analogues have revealed that the Z-isomer is moderately more active than the E-isomer at inhibiting in vitro tumor cell growth, suggesting that specific protein interactions may be important. Substitution of the terminal end allyl groups in ajoene for alkyl, aromatic, or heteroaromatic groups produces some analogs with superior in vitro anticancer activity to ajoene, opening up the way to developing ajoene-based anticancer agents.